2.1 T CELL GROWTH FACTORS AND RECEPTORS
T cells secrete a variety of polypeptides affecting immunoregulation of hematopoietic cells and are themselves subject to regulation by hormone peptides interacting with specific receptors on their cell surface Interleukin 2, originally termed T cell growth factor, is synthesized and secreted by antigen- or lectin-activated T lymphocytes in the presence of macrophage-derived interleukin-1 and must interact with specific high-affinity membrane receptors to exert its biological effects (Smith, K. A., 1980, Immunol. Rev. 51:337-357; Leonard, W. J., et al., 1983, Proc. Natl. Acad Sci. U.S.A. 80:6957-6961). The interleukin 2 receptor (IL2R, Tac antigen) is not present on the surface of resting T or B lymphocytes. Upon activation by specific antigens or mitogens, T cell proliferation is mediated by an autocrine mechanism whereby activated cells secrete interleukin 2 (IL-2) and also express cell surface receptors for IL-2 (IL2R) (Mier, J. W., and Gallo, R. C., 1980, Proc. Natl. Acad. Sci. U.S.A. 77:6134; Robb, R. J., et al., 1981, J. Exp. Med. 154:1455; Leonard, W. J., et al., 1982, Nature 300:267; Meuer, S. C., et al., 1984, Proc. Natl. Acad. Sci. U.S.A. 81:1509; Tsudo, M. et al., 1984, J. Exp. Med. 160:612-617; Waldmann, T. A., et al., 1984, J. Exp. Med 160: 1450-1466).
Interaction of IL-2 with its cell surface receptor results in a continuous T cell proliferation (Greene, W. C. K. A., 1984, Ann, Rev. Immunol. 2:319-333). Measurement of IL2R provides information on the state of immune activation of the lymphoid population. This has been accomplished by measuring IL2R on cell surfaces using flow cytometry or fluorescence microscopy. Using monoclonal antibodies which define the IL-2 receptor, altered IL-2 receptor expression has been reported in a number of immune abnormalities (Greene and Leonard, supra; Depper, J. M., et al., 1984, J. Immunol. 133:1691-1695). Membrane IL2R has been found on certain B- or T-cell malignancies including Burkitt's lymphoma (Waldmann, T. A., et al., 1984, J. Exp. Med. 160:1450-1466), hairy cell leukemia (Waldmann et al., supra; Korsmeyer, S. J., et al., 1983, Proc. Natl. Acad. Sci. U S.A. 80:4522-4526), and human T cell leukemia virus (HTLV)-I-associated adult T cell leukemia (Depper, J. M., et al., 1984, J. Immunol. 133:1691-1695). The function of 25 cellular IL2R in lymphoid malignancies has not been fully elucidated. Several cases of common, pre-B or T cell acute lymphoblastic leukemia (ALL) have been induced to express IL2R after in vitro activation (Touw, I., et al., 1985, Blood 66:556-561; Touw, I., et al , 1986, Blood 68:1088-1094; Matsuoka, M., et al., 1986, Leuk. Res. 10:597-603) and, in some cases, interleukin 2 stimulated subsequent colony formation of neoplastic progenitor cells in vitro (Touw, 1985, supra; Touw, 1986, supra).
Leukemia cells from some patients with T cell chronic lymphocytic leukemia were shown to have the receptors and a good proliferative response to exogenous interleukin 2 (Uchiyama, T., et al., 1985, J. Clin. Invest. 76:446-453; Tsudo, M., 1986, Blood 67:316-321). However, HTLV-1 associated adult T cell leukemia constitutively expressed high levels of cell surface IL2R but had no or very poor proliferative responses to interleukin 2 (Uchiyama, 1985, supra; Arya, S. K., et al., 1984, Science 223:1086-1087). Ebert et al. (1985, Clin. Immunol. Immunopathol 37:283-297) have reported that T cells from patients with AIDS virus lack the ability to express IL2R on their surface even when the cell is activated.
Secondary signals in T cell activation such as interleukin-1 (IL-1) are provided by monocytes or other accessory cells, and are required for IL-2 secretion (Schmidtke, J. R., and Hatfield, S., 1976, J. Immunol. 116:357; Maizel, A. L., et al., 1981, J. Exp Med. 153:470; Williams, J. M., et al., 1985, J. Immunol 135:2249).